1-Hydroxybenzotriazole → HCID 90416011, compound

HRID 513220Notes

Reaction equation

HRID 513220 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:11]3[CH2:12][C@H:13]4[NH:17][C@@H:16]([C:10]3=[N:9][N:8]=2)[CH2:15][CH2:14]4)=[CH:4][CH:3]=1.[Cl:18][C:19]1[C:20]([C:28]([F:31])([F:30])[F:29])=[N:21][CH:22]=[CH:23][C:24]=1[C:25](O)=[O:26].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:11]3[CH2:12][C@H:13]4[N:17]([C:25]([C:24]5[CH:23]=[CH:22][N:21]=[C:20]([C:28]([F:31])([F:29])[F:30])[C:19]=5[Cl:18])=[O:26])[C@@H:16]([C:10]3=[N:9][N:8]=2)[CH2:15][CH2:14]4)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 674623353-Chloro-2-(trifluoromethyl)pyridine-4-carboxylic acidHCID 90413576HCID 90413576, compound

Product 1

HCID 90416011HCID 90416011, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (6S,9R)-3-(5-chlorothiophen-2-yl)-6,7,8,9-tetrahydro-5H-6,9-epimino[1,2,4]triazolo[4,3-a]azepine (Example 55, step b) (35 mg, 0.132 mmol) in DCM (2 mL) was added 3-chloro-2-(trifluoromethyl)-4-pyridinecarboxylic acid (30 mg, 0.132 mmol) followed by HOBt (12 mg, 0.09 mmol), EDCl (38 mg, 0.197 mmol) and TEA (0.04 mL, 0.263 mmol). The reaction was stirred at room temperature overnight and then loaded directly on a SiO2 column eluting with IPA/EtOAc to afford the title compound (53 mg, 85%). MS (ESI): mass calcd. C18H12Cl2F3N5OS, 473.01; m/z found, 473.8 [M+H]+. 1H NMR (500 MHz, CDCl3): 8.75-8.59 (m, 1H), 7.68-7.30 (m, 1H), 7.26-7.13 (m, 1H), 7.03-6.92 (m, 1H), 5.46-5.31 (m, 1H), 4.98-4.87 (m, 1H), 4.65-4.50 (m, 1H), 4.25-3.94 (m, 1H), 2.63-2.23 (m, 3H), 2.00-1.86 (m, 1H).

Workup

  1. washeluting with IPA/EtOAc

Sources & evidence

ORD record
ord-1a9cba0d19344561922856f6be895e72
Source dataset
uspto-grants-2015_08
Patent number
US09102686B2

Reaction notes

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